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三甲基酸盐作为交叉合的甲基化剂:一种缓释机制,用于甲基化
Zhi-Tao He1, Haoquan Li1, Alexander M Haydl1
1Department of Chemistry , University of California , Berkeley , California 94720 , United States.
Journal of the American Chemical Society
|November 14, 2018
概括
这项研究引入了一种新的铜催化甲基化方法,使用的是温和且无毒的试剂 - - 三甲基酸盐. 这种高效的过程使药物化合物中惰性C-H键的功能化成为可能.
科学领域:
- 有机化学
- 催化剂
- 医学化学
背景情况:
- 甲基对分子的生物活性有很大的影响.
- 传统的甲基化方法通常使用苛刻或有毒的试剂.
- 需要更温和,更安全,更有效的甲基化策略.
研究的目的:
- 开发一种新的,高效的铜催化甲基化.
- 在合反应中使用三甲基酸盐作为温和且无毒的甲基化剂.
- 建立一种用于功能化的惰性C-H键的新方法.
主要方法:
- 使用三甲基酸盐的铜和联合催化甲基化.
- 化和随后甲基化的组合.
- 扩大到200mmol的反应以证明可靠性.
- 涉及三甲基和化催化剂的机制研究.
主要成果:
- 在用三甲基酸盐甲基化和异甲基酸中获得高产量.
- 与传统的甲基化剂如MeOTs或MeI相比,已经证明了优异的产量.
- 成功地将该方法应用于四种药用活性化合物的晚期甲基化.
- 机械研究显示,三甲基酸盐缓慢释放甲基化物.
结论:
- 开发的方法提供了一种新的,高效和温和的甲基合成策略.
- 化和三甲基化的组合提供了一种多用途的途径来功能化惰性结.
- 反应的可靠性和温和条件使其适用于药物化学的后期功能化.
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